Microscopy Technique Tracks Ribosome Activity

Researchers from the Tanenbaum group at the Hubrecht Institute have developed a novel microscopy technique to observe ribosome activity in cells. This method allows scientists to track individual ribosomes as they convert mRNA into proteins. In a phenomenon they call "ribosome cooperativity," the team discovered that ribosomes can support one another when encountering translation challenges.

Their findings, published in Cell, provide valuable insights into mRNA translation and protein synthesis and offer a tool for other researchers to explore these fundamental cellular processes.

Watching Ribosomes in Action

Certain mRNA sequences present challenges during translation into proteins, and the mechanisms ribosomes use to navigate these difficult sections remain largely unknown.

“We wanted to develop a new imaging technology to better understand how ribosomes perform their tasks,” 

Maximilian Madern, the study’s lead author from the Hubrecht Institute.

With this technique, scientists can now track individual ribosomes in real-time during mRNA translation. A visualization of this process shows ribosomes becoming brighter as they actively translate RNA.

The team has already uncovered new insights using this approach. “We observed that individual ribosomes move at slightly different speeds and sometimes pause for extended periods,” noted Sora Yang, the study’s second lead author.

Ribosomes Getting Stuck

Differences in translation speed can lead to ribosome collisions, which may slow protein production. Detecting these variations was a challenge, so the researchers collaborated with computational scientists from Marianne Bauer’s group at TU Delft’s Department of Bionanoscience. Their expertise confirmed that ribosomes indeed operate at varying speeds.

The study also revealed an important finding about ribosome collisions. When ribosomes collide due to speed differences or challenging RNA segments, the cell’s quality control mechanisms do not immediately respond. “Normally, these mechanisms would remove collided ribosomes, but they only activate if a collision persists for several minutes,” explained Madern.

Collisions May Be Beneficial

Contrary to previous assumptions, the researchers found that brief ribosome collisions might actually be advantageous. This phenomenon, termed "ribosome cooperativity," suggests that ribosomes assist one another in overcoming difficult-to-translate RNA regions.

“This ability to tolerate short collisions on problematic RNA sections helps ensure continuous protein production,” added Madern.

Applications and Future Research

This new technology allows researchers to analyze ribosome behavior at an individual level, offering deeper insights into cellular functions and protein synthesis. Understanding the dynamics of mRNA translation could have important implications for studying both normal cellular processes and disease-related disruptions in protein production.

Source:
Journal reference:

Yang, S., et al. (2025) Long-term imaging of individual ribosomes reveals ribosome cooperativity in mRNA translation. Cell. doi.org/10.1016/j.cell.2025.01.016

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